PMID- 22353757
OWN - NLM
STAT- MEDLINE
DCOM- 20120921
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 37
IP  - 7
DP  - 2012 Jun
TI  - Selective DNA methylation of BDNF promoter in bipolar disorder: differences among 
      patients with BDI and BDII.
PG  - 1647-55
LID - 10.1038/npp.2012.10 [doi]
AB  - The etiology of bipolar disorder (BD) is still poorly understood, involving 
      genetic and epigenetic mechanisms as well as environmental contributions. This 
      study aimed to investigate the degree of DNA methylation at the promoter region 
      of the brain-derived neurotrophic factor (BDNF) gene, as one of the candidate 
      genes associated with major psychoses, in peripheral blood mononuclear cells 
      isolated from 94 patients with BD (BD I=49, BD II=45) and 52 healthy controls. A 
      significant BDNF gene expression downregulation was observed in BD II 0.53+/-0.11%; 
      P<0.05), but not in BD I (1.13+/-0.19%) patients compared with controls (CONT: 
      1+/-0.2%). Consistently, an hypermethylation of the BDNF promoter region was 
      specifically found in BD II patients (CONT: 24.0+/-2.1%; BDI: 20.4+/-1.7%; BDII: 
      33.3+/-3.5%, P<0.05). Of note, higher levels of DNA methylation were observed in BD 
      subjects on pharmacological treatment with mood stabilizers plus antidepressants 
      (34.6+/-4.2%, predominantly BD II) compared with those exclusively on 
      mood-stabilizing agents (21.7+/-1.8%; P<0.01, predominantly BD I). Moreover, among 
      the different pharmacological therapies, lithium (20.1+/-3.8%, P<0.05) and 
      valproate (23.6+/-2.9%, P<0.05) were associated with a significant reduction of DNA 
      methylation compared with other drugs (35.6+/-4.6%). Present findings suggest 
      selective changes in DNA methylation of BDNF promoter in subjects with BD type II 
      and highlight the importance of epigenetic factors in mediating the onset and/or 
      susceptibility to BD, providing new insight into the mechanisms of gene 
      expression. Moreover, they shed light on possible mechanisms of action of 
      mood-stabilizing compounds vs antidepressants in the treatment of BD, pointing 
      out that BDNF regulation might be a key target for their effects.
FAU - D'Addario, Claudio
AU  - D'Addario C
AD  - Department of Biomedical Sciences, University of Teramo, Teramo, Italy.
FAU - Dell'Osso, Bernardo
AU  - Dell'Osso B
FAU - Palazzo, Maria Carlotta
AU  - Palazzo MC
FAU - Benatti, Beatrice
AU  - Benatti B
FAU - Lietti, Licia
AU  - Lietti L
FAU - Cattaneo, Elisabetta
AU  - Cattaneo E
FAU - Galimberti, Daniela
AU  - Galimberti D
FAU - Fenoglio, Chiara
AU  - Fenoglio C
FAU - Cortini, Francesca
AU  - Cortini F
FAU - Scarpini, Elio
AU  - Scarpini E
FAU - Arosio, Beatrice
AU  - Arosio B
FAU - Di Francesco, Andrea
AU  - Di Francesco A
FAU - Di Benedetto, Manuela
AU  - Di Benedetto M
FAU - Romualdi, Patrizia
AU  - Romualdi P
FAU - Candeletti, Sanzio
AU  - Candeletti S
FAU - Mari, Daniela
AU  - Mari D
FAU - Bergamaschini, Luigi
AU  - Bergamaschini L
FAU - Bresolin, Nereo
AU  - Bresolin N
FAU - Maccarrone, Mauro
AU  - Maccarrone M
FAU - Altamura, A Carlo
AU  - Altamura AC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120222
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antipsychotic Agents/pharmacology/therapeutic use
MH  - Bipolar Disorder/drug therapy/*genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - *DNA Methylation
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Promoter Regions, Genetic
PMC - PMC3358733
EDAT- 2012/02/23 06:00
MHDA- 2012/09/22 06:00
PMCR- 2013/06/01
CRDT- 2012/02/23 06:00
PHST- 2012/02/23 06:00 [entrez]
PHST- 2012/02/23 06:00 [pubmed]
PHST- 2012/09/22 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - npp201210 [pii]
AID - 10.1038/npp.2012.10 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2012 Jun;37(7):1647-55. doi: 10.1038/npp.2012.10. Epub 
      2012 Feb 22.